Efforts to determine normal functions for protein-tyrosine kinases encoded by human fgr and related proto-oncogenes have focused on the isolation of cDNA molecules representing their transcriptional units and complete coding sequences. We have isolated and sequenced human c-fgr and fyn cDNAs and have deduced the primary amino acid sequence of their encoded product. These findings have made it possible to identify the products of both genes, designated p55 c-fgr and p59 fyn. These gene products are protein-tyrosine kinases with conserved catalytic domains and unique amino terminal regions. We have shown that expression of the human c-fgr gene is limited to normal monocytes, granulocytes, macrophages and Epstein- Barr virus-infected B lymphocytes. Cultured granulocyte precursor cells express c-fgr mRNA only when induced to differentiate. Kinetic studies of p55 c-fgr expression in differentiating granulocytic cells imply that this protein functions on mature cells that no longer are capable of proliferating.